• DNA study enlighten us on how we maintain healthy blood sugar levels after meals

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    DNA study enlighten us on how we maintain healthy blood sugar levels after meals

    The researchers used mouse cell lines to analyse particular genes in and around these loci to explore for additional genes that may play a role in glucose regulation. color:#333333">

    color:#333333">Digital Desk: A study of over 55,000 people's DNA from around
    the world has given insight on how humans maintain appropriate blood sugar
    levels after eating, with implications for our knowledge of how the process
    goes awry in type 2 diabetes.



    color:#333333">The findings, which were published today in Nature Genetics,
    could help guide future treatments for type 2 diabetes, which affects over 4
    million individuals in the United Kingdom and over 460 million people
    worldwide.



    Older age, being
    overweight or obese, physical inactivity, and genetic susceptibility all
    contribute to an increased risk of type 2 diabetes. Type 2 diabetes, if left
    untreated, can cause complications such as eye and foot difficulties, nerve
    damage, and a higher risk of heart attack and stroke.



    color:#333333">Insulin, a hormone that regulates blood sugar - glucose -
    levels, is a major player in the development of the illness. People with type 2
    diabetes are unable to properly manage their glucose levels, either because
    they do not secrete enough insulin when glucose levels rise, such as after
    eating a meal, or because their cells are less susceptible to insulin, a
    condition known as "insulin resistance."

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    Most insulin resistance
    research to far have concentrated on the fasting state - that is, several hours
    after a meal - when insulin is primarily working on the liver. However, we
    spend the most of our time in the fed state, during which insulin effects on
    our muscle and fat tissues.



    The molecular mechanisms behind insulin resistance following a 'glucose
    challenge' - such as a sugary drink or meal - are thought to play a significant
    role in the development of type 2 diabetes. Nonetheless, these mechanisms are
    poorly understood.



    An multinational team of scientists looked for important genetic
    variations that influenced insulin levels measured two hours after a sugary
    drink using genetic data from 28 research including over 55,000 subjects (none
    of whom had type 2 diabetes).



    Following the sugary drink, the researchers discovered ten additional
    loci - or sections of the genome - connected with insulin resistance. Eight of
    these regions also had a higher incidence of type 2 diabetes, emphasising their
    significance.



    One of these newly discovered loci was found within the gene that codes
    for GLUT4, a crucial protein that transports glucose from the blood into cells
    after eating. This locus was linked to lower levels of GLUT4 in muscle tissue.



    The researchers used mouse cell lines to analyse particular genes in and
    around these loci to explore for additional genes that may play a role in
    glucose regulation. This resulted in the identification of 14 genes involved in
    GLUT 4 trafficking and glucose uptake, nine of which had never previously been
    related to insulin control.



    Further research revealed that these genes altered the amount of GLUT4
    located on the cell's surface, most likely via modifying the protein's ability
    to migrate from within the cell to the cell's surface. The less GLUT4 that
    reaches the cell's surface, the worse the cell's ability to take glucose from
    the blood.



    Dr. Alice Williamson, a PhD student at the Wellcome-MRC Institute of
    Metabolic Science, said, "What's exciting about this is that it shows how
    we can go from large scale genetic studies to understanding fundamental
    mechanisms of how our bodies work - and in particular how, when these
    mechanisms go wrong, they can lead to common diseases such as type 2
    diabetes."



    Given that problems regulating blood glucose after a meal can be an
    early indicator of an elevated risk of type 2 diabetes, the researchers are
    optimistic that uncovering the mechanisms involved can lead to innovative
    treatments in the future.



    "Our findings open up a
    potential new avenue for the development of treatments to stop the development
    of type 2 diabetes," said Professor Claudia Langenberg, Director of the
    Precision Healthcare University Research Institute (PHURI) at Queen Mary
    University of London and Professor of Computational Medicine at the Berlin
    Institute of Health in Germany. It also demonstrates how genetic studies of
    dynamic challenge tests can provide vital information that would otherwise be
    buried."



    Wellcome, the Medical Research
    Council, and the National Institute for Health and Care Research all provided
    funding for the study.